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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibodies (MoAbs) reacting with bovine leukocyte membrane antigens have been prepared by fusion of mouse myeloma cells (SP2/0.Ag.14) and spleen cells of mice immunized with various cell types. Three of these MoAbs detected membrane components showing the typical structure of class I MHC molecules; indeed, immunoprecipitation studies revealed that these components were proteins composed of two subunits of 44,000 and 12,000 daltons apparent molecular weight. The density of these antigens in the cells of various leukocyte lineages was determined by solid phase radioimmunoassay, immunogold staining and cytofluorometry. Their expression seemed similar to that of class I molecules in other species, namely heavy on the mononuclear blood cells and weaker on the neutrophils and platelets. The eosinophils appeared more positive than the neutrophils, while the erythrocytes were negative. Cross-inhibition and sequential immunoprecipitation experiments demonstrated that these MoAbs recognised different epitopes either on a single molecule or on cross-reacting molecules. One antibody appeared to be raised against the monomorphic bovine beta-2-microglobulin, while the two other antibodies detected the heavy chain of polymorphic class I-like products. The authors propose that the BoLA class I polymorphism should be studied by determination of the fixation ratio of the monomorphic anti-beta 2M versus the polymorphic anticlass I antibodies amongst the animals.
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PMID:Production and characterization of monoclonal antibodies raised against BoLA class I antigens. 309 53

Studies from this laboratory have indicated that isologous myeloma protein 315 (M315, isotype IgA, lambda 2) elicits T helper cells which recognize processed forms (peptides) of its V-domains and that recognition is controlled by H-2 linked immune-response (Ir) genes (J Exp Med 1982; 155:1587-96; Eur J Immunol 1986; 16:889-93). We now report that adjuvant-free soluble M315, particularly the mildly reduced and alkylated form, stimulates a T-dependent antibody response mainly specific for M315's paired V-domains. A small subset of the antibodies appeared to recognize the C-region of IgA, thus being analogous to rheumatoid factors (RF). On the basis of these observations, we propose that one pathway to RF production depends on T helper cells that interact directly with RF-producing B cells across peptide-MHC bridges. These peptides are envisaged to be derived from hypervariable regions of IgG V-domains, and they are therefore called "idiotypic peptides". This hypothesis assumes that the number of different idiotypic peptides is so large that the immune system has not developed tolerance to all of them.
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PMID:Are idiotypic peptides from variable domains critical for T-dependent production of rheumatoid factors? 326 65

Background responses have been assessed by fusing lipopolysaccharide- (LPS) stimulated spleen cells from unimmunized mice with MOPC 315.43 myeloma cells and screening the hybrids for the production of antibody against chicken red blood cells (CRBC). Clones specific for CRBC represented about 1% of total hybrid clones (1000 to 5000 clones were obtained per mouse). The majority of the anti-CRBC clones (greater than 95%) secreted antibody against polymorphic CRBC determinants (present on CRBC from some but not all chickens) rather than species-specific determinants present on all CRBC. Some of the polymorphic determinants were linked to the B locus (the MHC of the chicken) and some were non-B antigens. The relative amount of these 2 categories varied slightly according to the mouse strain. These results agree well with the specificities of natural mouse antibody and rosette-forming spleen cells. The response of immunized mice against CRBC and human RBC was also selective for polymorphic determinants. These results have considerable importance for the use of xenogeneic RBC as "standard" antigens, and are interpreted in terms of a model for the advantages of genetic polymorphism as a protection against antigen mimicry by parasites.
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PMID:The high background immune reactivity of mice to polymorphic determinants on xenogeneic erythrocytes: theoretical and practical implications. 617 71

BALB/c Lyt-1+ cells that proliferate in response to NP-modified BALB/c Ig fail to respond to BALB/c Ig modified by a different hapten, TNP. By contrast, when NP-modified BALB/c Ig is used as the immunogen in C.B-20 mice, a strain congenic with BALB/c but expressing the Ighb allotype of C57BL/6 (B6), a partial cross-reaction between NP- and TNP-BALB/c Ig is observed. Similarly, strains expressing different Igh haplotypes also show distinct reactivities toward NP-B6 Ig and NP-modified myeloma proteins. Thus, the proliferative response to NP-modified Ig is regulated by Igh-linked genes. In this paper, we also characterize the T cell proliferative response to IgG2a of the b allotype. We show that allotypic determinants on this molecule are recognized in association with self MHC-encoded gene products and that responsiveness is controlled by MHC-linked Ir genes. Thus, products of MHC-linked genes also influence the activity of Ig-recognizing T cells. Taken together, experiments described in this report suggest that T cells directed against immunogenic determinants on antibody molecules are governed by the same rules as T cells that respond to conventional antigens.
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PMID:Influence of Igh-C- and MHC-linked genes on the activity of immunoglobulin-recognizing T cells. 619 Aug 99

Five monoclonal antibodies reacting with class I MHC antigens were produced by fusing lymphocytes from WF (RT1u) rats immunized against DA (RT1a) rats with P3-X63-Ag8.653 myeloma cells. Sequential immunoprecipitation studies with the mAb and the WF anti-DA alloantiserum demonstrated the presence of four different class I molecules: all four molecules were reactive with the alloantiserum; three of them contained the determinant for mAb 155; two of the latter three molecules shared the determinants for mAb 3, 56 and 60, and one of these two molecules also contained the determinant for mAb 118. The four molecules could be isolated from the antigen preparation by sequential immunodepletion first with 118, next with 3, then with 115 and finally with the alloantiserum or by sequential absorption with affinity columns of Sepharose 4B coupled to the antibodies. The three antigens which were sequentially isolated with the mAb 118, 3, and 155, respectively, were analysed by SDS-PAGE after digestion with Staphylococcus aureus V8 protease, and they showed differences in peptide patterns. The relative amounts of the antigens expressed on red blood cells and on lymphocytes were different based on the results of sequential isolation and indirect cellular radioimmunoassay: the antigen which reacted with both mAb 3 (and 56 or 60) and 155 was the major class I antigen on red blood cells, and the antigen which reacted with mAb 118, 3 (and 56 or 60) and 155 was the major class I antigen on lymphocytes.
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PMID:Immunochemical evidence for multiple class I antigens coded by the MHC of the rat (RT1) and their differential expression on red blood cells and lymphocytes. 619 15

We previously reported that B lymphocytes obtained from BALB/c mice that had been immunized with M104E myeloma protein have an idiotype-specific enhancing activity for anti-dextran B1355S antibody responses in vivo. The enhancing cells were Thy-1-, Lyt-1-,2-, nylon wool-adherent and rabbit anti-mouse immunoglobulin (RAMG) dish adherent. The in vitro analysis described in this report also revealed that the enhancing cells had a B cell phenotype and were specifically enriched in M104E or J558 myeloma protein-coated dishes but not by irrelevant monoclonal antibodies. The significance of these B-B cell interactions were analyzed in vitro by using various Igh-1 and H-2 congeneic strains of mice. The idiotype immune B lymphocytes obtained from BALB/c and BAB-14 could enhance the antidextran antibody responses of BALB/c B lymphocytes in an idiotype-specific manner. On the other hand, C.AL-20 and CB-20 strains could not induce the idiotype-specific enhancing B cell activity in dextran-immune BALB/c B cells. These results suggest that the capability of enhancing B cell induction is related to the producibility of the respective idiotype in that strain of mice. Moreover, the B cells obtained from BALB/c mice immune to the idiotype cooperated well with the dextran-immune B cells of BALB/c but not of BALB.K and vice versa. These results indicate that successful cooperation between those two types of B lymphocytes requires the same MHC haplotype. The roles of these genetically restricted cellular interactions in the immune system are discussed.
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PMID:Regulation of immune responses via genetically-restricted cellular interactions. I. Augmentation of antibody responses by idiotype-specific enhancing B lymphocytes. 620 63

The major histocompatibility complex of the rat (RTl) is composed of at least five subregions. They are RTl-A,B,C,D and E regions. RTl-A,E and RTl-B,D regions encode class I and class II alloantigens, respectively. The RTl-C region encodes antigens which are similar to class I alloantigens and they are the homologue of mouse Qa-Tla antigens. A monoclonal antibody (X81-5C9) was produced against a rat B-cell leukemia, KNL-14. The KNL-14 cells were injected to a congenic rat, WKA. 1A(ACI). Spleen cells taken from the congenic rat were hybridized with mouse myeloma cell line P3.X63.Ag8.653. The monoclonal antibody lysed over 80% of nylon wool (N. W) adherent cells of lymph nodes, 25-30% of unseparated lymph node cells and/or spleen cells, and approximately 15-20% of peripheral blood lymphocytes of WKAH strain of rats. Only a portion (30-40%) of N. W. adherent cells of the peripheral blood lymphocytes was killed. Bone marrow cells, thymus cells and N. W. nonadherent cells were not lysed by the antibody. Macrophages, fetus, thymus and kidney homogenates could absorb the reactivity, whereas RBC, epidermal cells, brain, liver, testis could not absorb the cytotoxicity. A survey for the strain distribution of the antigen disclosed positive strains such as WKAH, W/Hok, LEJ, WKA. 1J (LEJ), ALB, WKA. 1B (ALB), BUF, BN, LEW, F344, W. 1L (F344) and KYN rats. The negative strains were NIG-III, WF, WKA. 1U WF), SDJ, W. 1U (SDJ), TO, W. 1T(TO), ACI, WKA. 1A(ACI), BDIX, WKA. 1DV1 (BDIX) and PVG/c rats. Immunochemically, the antibody precipitated antigens that gave two major bands on the SDS-PAGE. The heavy chain has an apparent molecular weight of 30 KD, which shifted to 33 KD under reducing conditions. The light chain has an apparent molecular weight of 12 KD. From these data a monoclonal antibody X81-5C9 is considered to detect a rat MHC (RTl) gene product which is different from the classic class I or class II cell surface antigens. It may be one of RTl-C antigens expressed mainly on B-cells. The characteristic feature of rat RTl-C antigens were discussed in relation to mouse Qa-Tla antigens.
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PMID:[A new B-cell alloantigen of the rat]. 623 70

Somatic cell hybridization between nonmetastatic tumor cells and normal cells of the lymphoreticular system results in hybrid cells manifesting metastatic properties of defined target organ specificity. Thus, fusion of the nonmetastatic BALB/c originated NSI plasmacytoma with C57BL B lymphocytes resulted in hybridomas, each of which were metastatic. Of 10 hybridomas, 7 generated metastases in the spleen and liver, whereas 3 generated liver metastases. The generation of liver metastases by hybridomas which homed to both spleen and liver, but not by those which homed to the liver only, was controlled by the spleen. The acquisition of metastatic properties via somatic cell fusion seems to represent a general principle, in which the normal partner determines the target organ specificity for the metastatic growth. Thus, fusion of SP2/O myeloma cells with syngeneic B lymphocytes also resulted in a hybrid cell metastasizing to the spleen and liver, yet a somatic hybrid between NSI and a macrophage or dendritic-like cell metastasized to the lung. Cell surface molecules encoded by the genome of the normal partner was demonstrated to control the target organ specificity: antibodies against MHC-encoded antigens of the normal B cell partner prevented the generation of metastases by hybridomas metastasizing to the spleen and liver, but not by those metastasizing to the liver only. This is in accordance with the function of MHC molecules on lymphocytes in controlling their homing to lymphoid organs. Hybridomas of T cell lymphomas also manifested metastatic properties. Analysis of the cell surface Thy-1 antigens of a hybridoma (DCH10), produced via somatic fusion between BW5145 lymphoma and a putative macrophage cell indicated that cells of liver metastases (DCH10-Li) generated by the hybrid cells might have undergone further somatic cell fusion in vivo with host (T?) cells. These cells have acquired new metastatic properties, generating metastases in spleen, liver and kidneys. In fact, even the inoculation of the parental BW lymphoma cells resulted in a case of liver metastasis (BW-Li). Such BW-Li cells, upon reinoculation, also generated metastases in the spleen, liver and kidneys. Analysis of the Thyl phenotype indicated that BW-Li cells may also have undergone somatic cell fusion in vivo with host (T?) cells, resulting in the acquisition of metastatic properties. The pattern of cell-cell interactions (adhesion, infiltration) with liver cell monolayers of BW-Li cells and of DCH10-Li (T-cell lymphomas) was identical, and differed from cells of liver metastases of the myeloma-B cell hybridomas which might be based on responses to liver growth signals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nonmetastatic tumor cells acquire metastatic properties following somatic hybridization with normal cells. 637 Apr 19

Hybridoma cell lines secreting antibodies to mouse H-2 or Ia antigens have been generated by fusing mouse immune lymphocytes with appropriate myeloma lines. Among the 11 established clones reported here, nine produce anti-H-2 antibodies and two produce anti-Ia antibodies. The specificities and cross-reactions of these monoclonal antibodies have been studied in detail. One hybridoma antibody reacted only to Kk antigens without any detectable cross-reactions, thus suggesting reaction to a private specificity of the Kk molecule. All other anti-H-2 hybridoma antibodies appeared to detect public specificities as defined either by reactions with products of more than one H-2 locus or with different alleles at one or more loci. The two anti-Ia antibodies both reacted with I-E/C products, but exhibited different cross-reactivity patterns. Strain distribution analyses so far indicate that the public specificities detected by these monoclonal antibodies are considerably different from those that had been established by traditional serology. Since public specificities defined by the hybridoma antibodies must by definition represent cross-reactions, these findings may have important implications relating to the structure and evolution of MHC gene products.
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PMID:Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. 718 99

CTLs that recognize tumor Ags have been described in mice and humans, particularly for melanoma. These CTLs are CD8+, which is MHC-restricted. In contrast, in human carcinomas of the breast, pancreas, or ovary, and in multiple myeloma, CD8+ CTLs have been described that lyse targets expressing human MUC1 in a non-MHC-restricted manner. On the basis of these observations, we immunized mice with conjugates of mannan-human fusion protein, human mucin 1 (MUC1), which produced CD8+ CTLs. In contrast to the human anti-MUC1 CTLs found in cancer patients, the murine anti-MUC1 CTLs were clearly MHC-restricted, e.g., in inbred mice of the H-2-b, d, k, s, or z haplotypes; the H-2 restriction was also confirmed in H-2 congenic strains. Tests of H-2 recombinant strains demonstrated that MUC1 peptides were able to associate with D or K class I molecules of the b, d, or k haplotypes. Mice lacking MHC-class I molecules made weak CTL responses that were H-2Db-restricted, and in the class I H-2Kbm1 mutant strain, CTL restriction was also shown. Finally, cold target inhibition studies demonstrated that Kb and Db are recognized similarly, but Kk is less well recognized. Thus, anti-MUC1 CTLs induced by immunization of mice are different from those obtained from patients. The immunization of cancer patients with MUC1 peptides is now undergoing clinical trials and it will be of interest to observe whether the CTLs induced are HLA-restricted, not restricted, or whether both types of CTLs are produced.
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PMID:CTL in mice immunized with human mucin 1 are MHC-restricted. 759 17


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